POS0459 APTAMER-BASED PROTEOMIC SCREENING IN IDENTIFICATION OF PATHOGENIC SIGNAL PATHWAY AND URINARY BIOMARKERS ASSOCIATED WITH HISTOLOGICAL FINDINGS IN LUPUS NEPHRITIS
Authors: K. Hiramoto, S. Saito, H. Hanaoka, K. Suzuki, J. Kikuchi, H. Fukui, R. Takano, F. Miyoshi, N. Seki, K. Sugahara, Y. Kaneko, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2022)

Background The current gold standard for the diagnosis and classification, assessment of the severity of lupus nephritis (LN) is a renal biopsy. On the other hand, since the procedure is highly invasive, there is a pressing need to identify biomarkers for predicting the presence and its histological severity of LN. In addition, the background pathogenesis of each histological findings is not clearly understood. Objectives The purpose of this study was to elucidate the urine biomarkers for predicting the presence and the severity of histological findings of LN, and to search the pathogenic signal pathway. Methods Urine samples from 24 biopsy-proven active LN patients were initially screened for the levels of 1305 distinct human proteins using an aptamer-based-targeted proteomic assay. We developed histological scoring system based on ISN/RPS lesion definitions and classification, NIH activity and chronicity score. Two experienced evaluators assessed the histological scores. Cluster analysis and pathway analysis were performed. Results A total of 24 LN patients were included: 20 (83%) had a proliferative histological class (III or IV +/-V), 4 (17%) pure membranous (V). Through cluster analysis, several histological subgroups were extracted according to correlation with each histological finding, and proteins which corelated with each histological scores were analyzed. We focused on two subgroups: one in which including active glomerular histological findings (endocapillary hypercellularity, karyorrhexis, neutrophil infiltration, subendothelial deposits) and the other in which including interstitial histological findings (interstitial inflammation, interstitial fibrosis, tubular atrophy). Histological scores in the former group showed strong positive correlation with protein group which contained 59 proteins (Group A), including CCL21, CXCL10, VCAM1. Histological scores in the latter group corelated with another protein group which contained 85 proteins (Group B), including MCP-1, CCL11. Ingenuity Pathway Analysis showed 16 pathways (PDGF Signaling, Granulocyte Adhesion and Diapedesis, etc) were upregulated in Group A and 11 pathways (IL-17 signaling, Fibrosis signaling pathway, etc) upregulated in Group B. Among group A and group B urine proteins, those showed strong correlation between respective histological findings were validated with ELISA assays. Conclusion An aptamer-based-targeted proteomic assay screening by combining with renal histological scoring system suggested several urine proteins can predict the severity and the presence of major renal histological findings, and suggested to be related with the pathogenesis in patients with LN. Disclosure of Interests Kazuoto Hiramoto: None declared, Shuntaro Saito: None declared, Hironari Hanaoka: None declared, Katsuya Suzuki: None declared, Jun Kikuchi: None declared, Hiroyuki Fukui: None declared, Ryo Takano Employee of: Mitsubishi Tanabe Pharma Corporation Sohyaku, Fumihiko Miyoshi Employee of: Mitsubishi Tanabe Pharma Corporation Sohyaku, Noriyasu Seki Employee of: Mitsubishi Tanabe Pharma Corporation Sohyaku, Kunio Sugahara Employee of: Mitsubishi Tanabe Pharma Corporation Sohyaku, Yuko Kaneko: None declared, Tsutomu Takeuchi: None declared.